We propose to continue our multiscale mechanical analysis of bioengineered tissues. In the current grant, we have used our two-scale model, in which the microscopic scale represents the collagen fiber network, and the macroscopic scale represents the tissue as a whole; the two scales are fully coupled, and we have implemented the model in three dimensions and developed a biphasic formulation. A finite-element-based computational environment has been developed that allows solution of the model equations efficiently on up to 256 processors. In this renewal, we propose three major extensions to increase the power and applicability of our model: (1) Multiple components, allowing simulation of collagen-fibrin co-gels and tissues remodeled by entrapped cells, (2) Cellular contribution to mechanics, critical for describing cellularized engineered tissues, and (3) Failure mechanics, motivated by the need to make tissues that can withstand in vivo loads without failing and the lack of available tools to predict tissue failure based on composition and structure. Taken together, these steps will create a tool for rational engineering design of replacement tissues based on their functional requirements. Tissue engineering, the creation of replacements for damaged or diseased tissues, is an important area, especially for mechanical tissues such as artery, heart valve, and skin. A major impediment to advances in tissue engineering is our inability to design tissues as we design other engineered products. This project relates directly to public health because it would provide tools to help create the next generation of replacement tissues. PUBLIC HEALTH RELEVANCE: We continue to develop models that allow us to predict the mechanical behavior of bioengineered replacement tissues based on their structure and composition. The work will enable design of the next generation of engineered tissues by helping to determine what components, in what arrangement, are needed to achieve tissue properties similar to the native tissue. This project relates directly to public health, particularly to cardiovascular health, because of the need for mechanically functioning replacements for arteries and heart valves. [unreadable] [unreadable] [unreadable]